How gut bacteria may affect anxiety

Tiny molecules in the brain may help gut bacteria hijack people’s emotions.

Bacteria living in the human gut have strange influence over mood, depression and more, but it has been unclear exactly how belly-dwelling bacteria exercise remote control of the brain (SN: 4/2/16, p. 23). Now research in rodents suggests that gut microbes may alter the inventory of microRNAs — molecules that help keep cells in working order by managing protein production — in brain regions involved in controlling anxiety.

The findings, reported online August 25 in Microbiome, could help scientists develop new treatments for some mental health problems.

Mounting evidence indicates “that the way we think and feel might be able to be controlled by our gut microbiota,” says study coauthor Gerard Clarke, a psychiatrist at University College Cork in Ireland. For instance, the presence or absence of gut bacteria can influence whether a mouse exhibits anxiety-like behaviors, such as avoiding bright lights or open spaces.

Clarke and colleagues compared normal mice, whose gastrointestinal tracts were teeming with bacteria, with mice bred in sterile environments, whose guts didn’t contain any microbes. The researchers discovered that in brain regions involved in regulating anxiety — the amygdala and prefrontal cortex — microbe-free mice had an overabundance of some types of microRNA and a shortage of others compared with normal mice. After scientists exposed some sterilized mice to microbes, the rodents’ microRNA levels more closely matched those of normal mice.

The team also examined microRNAs in the amygdala and prefrontal cortex of rats whose gut bacteria had been decimated by antibiotics. These rats overproduced or underproduced some of the same microRNAs that were off-kilter in bacteria-free mice. The researchers suspect that gut bacteria affect their host’s anxiety levels by tampering with microRNAs in specific parts of the brain.

“I was a little surprised by the findings — in a positive way — because I think not many people so far have thought about microRNAs in this context,” says Peter Holzer, a neurogastroenterologist at the Medical University of Graz in Austria who wasn’t involved in the study. “It’s heading into a new area in gut-brain research that hasn’t been pursued.”

Researchers still aren’t sure how these bacteria dial microRNA production up and down in the brain. Maybe the microbes send signals along the vagus nerve, a kind of information highway that runs from gut to brain. Or perhaps bacteria churn out molecular by-products that provoke the immune system to produce chemicals that cause the brain to produce more or less of particular microRNAs. Outlining microbes’ mental manipulation scheme from start to finish “is still a work in progress,” Clarke says.

Next the team wants to see if probiotic drugs can cultivate certain types of bacteria in the gut, and therefore fine-tune microRNA levels in specific parts of the brain. If scientists can adjust microRNA abundances in a way that assuages anxiety, it could help lead to the development of new medications for psychiatric and neurological disorders.

MicroRNA-based medications may be unrealistic in the short term, though, says gastroenterologist Kirsten Tillisch of UCLA. “People tend to like to extrapolate these types of results to humans and start moving quickly towards clinical applications. It is just so tempting,” says Tillisch, who was not involved in the study. “But we know historically the translation from lab animal to human is hit-and-miss.”